Clinical Clues and Diagnostic Workup of Cardiac Amyloidosis

Abstract

Cardiac amyloidosis is increasingly recognized as an underlying cause of left ventricular wall thickening, heart failure, and arrhythmia with variable clinical presentation. Due to the subtle cardiac findings in early transthyretin cardiac amyloidosis and the availability of therapies that can modify but not reverse the disease progression, early recognition is vital. In light chain amyloidosis, timely diagnosis and treatment can significantly improve survival. In this manuscript, we review the clinical, imaging, and electrocardiographic clues that should raise suspicion for cardiac amyloidosis and provide a simplified diagnostic workup algorithm that ensures an accurate diagnosis. The evolution of the noninvasive diagnosis of cardiac amyloidosis has significantly influenced our understanding of disease prevalence, presentations, and outcomes. However, clinical recognition of clues and red flags remains the most important factor in advancing the care of patients with cardiac amyloidosis.

Keywords: aortic stenosis; bone scintigraphy; cardiac amyloidosis; cardiac magnetic resonance imaging; endomyocardial biopsy; heart failure; immunoglobulin light chain; left ventricular hypertrophy; systemic amyloidosis; transthyretin.

Figure 1

Simplified diagnostic algorithm for suspected cardiac amyloidosis. EKG: electrocardiogram; AL: immunoglobulin light chain; Heme: hematology; CMR: cardiac magnetic resonance imaging; Tc-99m PYP: technetium-99m pyrophosphate; SPECT: single-photon emission computed tomography; MGUS: monoclonal gammopathy of undetermined significance; ATTR/TTR: transthyretin; NT-proBNP: N-terminal prohormone of brain natriuretic peptide

Figure 2

Cardiac magnetic resonance imaging (CMR) of a patient presenting with dyspnea and found to have left ventricular hypertrophy. First set of images (A, B and E) were obtained prior to presenting to our practice. Image A shows concentric left ventricular hypertrophy. Due to abnormal gadolinium kinetics and selecting an inappropriately low inversion time, late gadolinium enhancement (B) short axis and (E) 4-chamber views were not interpretable. (D) Repeat CMR shows severe asymmetrical septal hypertrophy on 4-chamber view; with choosing an appropriate inversion time for late gadolinium enhancement imaging, there was global enhancement of the left ventricle (sparing anterior and anterolateral segments), right ventricle, and both atria (C, F). Image G shows significant expansion of the extracellular volume (ECV) fraction (51% in the septum), which can be reliably obtained even if late gadolinium imaging sequences are suboptimal.

Figure 3

Multimodality imaging in the workup of a 70-year-old patient who is a carrier for the p.V50M variant and who presented with exertional shortness of breath and palpitations. (A) Echocardiogram parasternal long-axis window showing normal left ventricular wall thickness. (B) Depressed longitudinal strain, particularly in the basal septal segments (absence of apical sparing pattern). (C) 99m-technetium pyrophosphate single photo emission computed tomography showing diffuse uptake of the tracer in the myocardium. (D) Cardiac magnetic resonance imaging with phase-sensitive inversion recovery sequences obtained 15 minutes post gadolinium show minimal late gadolinium enhancement, but dedicated sequences showed elevated native T1 (1130 millisecond, 1.5 Tesla) and extracellular volume fraction (39%).